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Phenotypes Associated with This Genotype
Genotype
MGI:2661730
Allelic
Composition
Ace2tm1Pngr/Y
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ace2tm1Pngr mutation (1 available); any Ace2 mutation (36 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight
• hearts show upregulation of hypertrophic disease markers ANF and BNP

cardiovascular system
• development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight
• hearts show upregulation of hypertrophic disease markers ANF and BNP
• slight thinning of the left ventricular wall resulting in mild dilation, 6 months of age
• ventricular dilation at 6 and 12 months of age
• progressive left ventricular dilation and reduced systolic function with increasing age
• age-dependent and progressive decline in cardiac function
• development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight
• young mice treated with the specific AT1 receptor blocker, irbesartan, until 12 months of age prevents the development of dilated cardiomyopathy at 6 months and persists until 12 months of age
• more severe at 6 months of age than at 3 months of age (J:77232)
• more severe in 6 month old males than in age matched female mutant mice (J:77232)
• decrease in fractional shortening and velocity of circumferential shortening corrected for heart rate, decreased peak aortic velocity corrected for heart rate (J:124548)
• rightward displacement of the pressure-volume curve indicating reduced systolic function (J:124548)
• echocardiography indicates increased left ventricular end diastolic and systolic dimension, decreased fractional shortening, decreased velocity of circumferential shortening corrected for heart rate, decreased peak aortic velocity corrected for heart rate, increased left ventricle end diastolic pressure, and decreased maximum and minimum first derivative of the left ventricle pressure (+dP/dt and dP/dt)
• increase in left ventricle end diastolic pressure
• reduced blood pressure observed at 6 months of age
• blood pressure was normal at 3 months of age
• 4-fold increase in neutrophil infiltration in the myocardium of aged mice
• however, no macrophage infiltration into the myocardium is seen
• treatment with irbesartan prevents neutrophil infiltration in the myocardium

cellular
• myocardial aldehyde levels are increased in mice indicating chronic myocardial oxidative damage
• treatment with irbesartan normalizes myocardial aldehyde levels

homeostasis/metabolism
• increase in expression of inflammatory cytokines, IL-1beta, IL-6, and MCP-1 in aged mice
• treatment with irbesartan prevents increased expression of inflammatory cytokines
• NADPH oxidase activity is increase in the left ventricle of 6 month old mice
• mice treated with irbesartan to block AT1 suppresses the increase in NADPH oxidase activity

muscle
• development of cardiomyopathy is associated with eccentric hypertrophy as indicated by increased left ventricle weight normalized to tibial length or body weight
• young mice treated with the specific AT1 receptor blocker, irbesartan, until 12 months of age prevents the development of dilated cardiomyopathy at 6 months and persists until 12 months of age
• more severe at 6 months of age than at 3 months of age (J:77232)
• more severe in 6 month old males than in age matched female mutant mice (J:77232)
• decrease in fractional shortening and velocity of circumferential shortening corrected for heart rate, decreased peak aortic velocity corrected for heart rate (J:124548)
• rightward displacement of the pressure-volume curve indicating reduced systolic function (J:124548)

immune system
• 4-fold increase in neutrophil infiltration in the myocardium of aged mice
• however, no macrophage infiltration into the myocardium is seen
• treatment with irbesartan prevents neutrophil infiltration in the myocardium
• increase in expression of inflammatory cytokines, IL-1beta, IL-6, and MCP-1 in aged mice
• treatment with irbesartan prevents increased expression of inflammatory cytokines

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
congestive heart failure DOID:6000 J:124548


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
01/24/2023
MGI 6.22
The Jackson Laboratory